反应详情

温度

110 °C

In a screw-capped vial are added MeOH (3.5 mL) and sodium metal (2 mg). After 10 min, valerolactam (16 mg, 0.16 mmole) is added. The solvent is removed under reduced pressure. To the residual solid are added 2-(4-bromophenyl)-1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulene (example 122A) (50 mg, 0.107 mmole), Pd(dba)2 (4.9 mg, 5.3 μmole), Xantphos (6.2 mg, 10.6 μmole), toluene (0.7 mL). The flask is evacuated and filled with argon and the reaction mixture is heated at 110° C. overnight. Water is added and pH adjusted to 10 with a few drops of 1N NaOH. The aqueous phase is extracted three times with CH2Cl2. The organic phase is dried over magnesium sulphate, filtered and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using (CH2Cl2:MeOH:NH4OH) with a gradient from (100:0:0) to (96.5:3.5:0.35) to give 1-{4-[1-methyl-4-(1-methylpiperidin-4-yloxy)-9,10-dihydro-4H-3,10a-diaza-benzo[f]azulen-2-yl]-phenyl}-piperidin-2-one.

1. customThe solvent is removed under reduced pressure
2. customThe flask is evacuated
3. additionfilled with argon
4. additionWater is added
5. extractionThe aqueous phase is extracted three times with CH2Cl2
6. dry with materialThe organic phase is dried over magnesium sulphate
7. filtrationfiltered
8. customthe solvent is removed under reduced pressure
9. customThe residue is purified by silica gel chromatography